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PubMed2004

Genomic imprinting of H19 in naturally reproduced and cloned cattle.

Animals produced from assisted reproductive technologies suffer from developmental abnormalities and early fetal death at a higher frequency than that observed in those produced by natural breeding. These symptoms are reminiscent of imprinting disruptions in the human and mouse, suggesting the possibility of perturbations in the expression of imprinted genes such as biallelic expression or silencing. H19 is one of the imprinted genes first identified in mice and humans, but its sequence and imprinting status have not been determined in cattle. In the present study, we obtained the majority of the bovine H19 gene sequence (approximately 2311 base pairs), identified a single nucleotide polymorphism (SNP) in exon 5 and determined the frequencies of different alleles containing the SNP. Our analysis demonstrated that, in cattle produced by natural breeding, H19 was indeed imprinted as shown by either predominant or exclusive expression of the maternal allele. We also analyzed the imprinting pattern of H19 in organs of four animals produced by somatic cell nuclear transfer that died shortly after birth or had developed abnormalities that necessitated immediate killing at birth. Three out of four cloned animals showed biallelic expression of H19, supporting our hypothesis that imprinting disruption is present in cloned animals that suffered from developmental abnormalities at birth. Examination of the expression of H19 in the offspring of a cloned animal produced by artificial insemination showed that the imprinting pattern in this animal was indistinguishable from those of control animals, suggesting that either imprinting disruptions in cloned animals are corrected through natural reproduction or that they are not present in healthy cloned animals capable of undergoing natural reproduction.

Alleles↗
PubMed2004

[Perinatal result of an institutional assisted reproduction program].

BACKGROUND: Assisted reproductive technology manipulates masculine gametes, embryos and implantation. It also aids the known or unknown factor of sterility without having the base problem correction as a target. In vitro fertilization and embryo transfer are among these techniques. OBJECTIVE: To describe the overall outcome and the final perinatal offspring after in vitro fertilization cycle in an institutional third level hospital. MATERIALS AND METHODS: IVF cycles were retrospectively analyzed from October 1999 to May 2004. Several variables were described like: age, fertilization rate, implantation and pregnancy rate, fetal status, time of gestation during labor, miscarriage follicle-stimulating hormone rate and take-home baby rate. Patients underwent hypophyseal supression with GnRH analog, using a long luteal phase protocol and stimulated with recombinant FSH. Overall data is expressed as average +/- standard deviation and percentage. RESULTS: 365 cycles were analyzed in 314 patients, average age was of 34 +/- 3.7 years, tubal factor was diagnosed in 63.3%, fertilization rate was of 60.4%, implantation rate of 37.1%, per transfer pregnancy rate of 25.1%, per transfer live born rate of 21.7%, multiple pregnancy rate of 29.3%, miscarriage rate of 28% and ectopic pregnancy rate of 4.8%. In 87.8% of the cases caesarean operation was made; multiple pregnancy offspring weighted more than 1250 g in 70% of them; 70.5% was born after 32 weeks of pregnancy; 90% was born live and with good prognosis. Glucose metabolism alterations were the most frequent maternal complication. CONCLUSION: Although the results obtained were similar to those of assisted reproduction centers, it suggests improving multiple pregnancy rate and abortion rate.

Adult↗
PubMed2006

Vitrification of mouse pronuclear oocytes with no direct liquid nitrogen contact.

The ability to routinely cryopreserve human oocytes and embryos represents a significant advancement in the field of assisted reproductive technology. Although the method of slow freezing is commonly employed, research on the alternative technique of vitrification is promising. Vitrification involves incubation of the cell in a cryoprotectant rich solution, which permits a glass-like state to occur almost instantaneously in liquid nitrogen. A number of different techniques have been invented for holding oocytes and embryos in the cryoprotectant solution during rapid vitrification and subsequent storage. Most of these involve direct contact with liquid nitrogen. Recently, concerns have been raised regarding the sterility of such a method and the potential of viral contamination from the liquid nitrogen. The present study shows that the previously reported Cryoloop method can be used to vitrify and store embryos without direct liquid nitrogen contact (during vitrification and storage). When such vitrified embryos are warmed, they are capable of subsequent development comparable with non-vitrified embryos.

Analysis of Variance↗
PubMed1998

Trends and international comparisons in infertility in circumpolar areas.

Infertility is an increasing problem for both individuals and societies. The number of couples seeking treatment for infertility is increasing each year, and public interest seems to be rising along with the new treatment methods and the improving results. Male infertility is also of great interest now that several studies suggest a deterioration in the quality of semen in many countries, Finland being an exception. The assisted reproductive technologies have improved tremendously since the first child conceived by in vitro fertilization was born in 1978. The new techniques include e.g. intrauterine insemination (IUI), gamete intrafallopian transfer (GIFT), in vitro fertilization (IVF), intracellular sperm injection (ICSI) and various combination treatments. These treatments are costly and both physically and emotionally stressful, and the success rate varies according to the aetiology of infertility, the age of the woman treated and the method used. More information is needed about the aetiology and incidence of fertility disorders as well as about the availability of treatment in the circumpolar areas and the couples' opinions of treatment. Our own study population, which was drawn form the northern Finland birth cohort for 1966, provides an outstanding opportunity to study these issues, since data are available for the whole life course of the individuals, dating back to prenatal life.

Adult↗
PubMed1994

Concurrent tuboplasty and assisted reproduction.

OBJECTIVE: To review and summarize the role of combining assisted reproductive technologies (ART) with lysis of adhesions and microsurgical tuboplasty in selected groups of patients. DESIGN: A retrospective analysis of the available literature and a review of the results of concurrent fimbriectomy reversal and ART. CONCLUSION: In a relatively few and highly selected patients, the concurrent use of ART and laparotomy or laparoscopy for lysis of adhesions and tuboplasty can more safely access the ovaries for oocyte retrieval and address associated problems such as pelvic pain while reducing cost. Examples of such cases include patients with ovaries in abnormal locations, on a congenital basis or after extensive bowel or urogenital reconstructive surgery. Because some procedures such as fimbriectomy reversal have a relatively low fecundity, there is potential for increasing cumulative pregnancy rates when ART and microsurgery are combined. The advantages of increased fecundity and cost-effectiveness must be weighed against the disadvantages of operating room scheduling and the potential surgical and anesthetic risks.

Fallopian Tube Diseases↗
PubMed1993

Increased risk of monochorionic twinning associated with assisted reproduction.

OBJECTIVE: To determine the incidence of monochorionic twinning in pregnancies resulting from assisted reproduction technologies (ARTs). METHODS: We reviewed our experience with 218 ART pregnancies achieved over 3 years. All patients underwent transvaginal ultrasound 26 and 36 days after oocyte retrieval. The presence of two yolk sacs or two fetal poles within one sac suggested monochorionicity, and was confirmed by follow-up ultrasound and placental pathology. The various ARTs were compared to determine if any method had an increased incidence of monochorionicity compared to any other method. Statistical analysis was performed employing Chi Square analysis. RESULTS: The incidence of monochorionicity in all gestations was 3.2% (8 times background rate); among multiple gestations it was 9.8%. The rates of monochorionicity for each ART appeared similar. CONCLUSION: The incidence of monochorionic twinning is increased in pregnancies resulting from ART. Careful ultrasound evaluation of such pregnancies for monochorionicity is strongly recommended, both for planning of prenatal care and when considering a multifetal pregnancy reduction procedure.

Chorion↗
PubMed2003

Generation of live fry from intraperitoneally transplanted primordial germ cells in rainbow trout.

Germ cell transplantation has tremendous applications in transgenic animal production, assisted reproductive technology, and germline stem cell research. Here, we report for the first time the production of individuals from intraperitoneally transplanted primordial germ cells (PGCs) in animals. To trace the behavior of exogenous PGCs in recipients, PGCs visualized by a green fluorescent protein gene were used as donors. The PGCs prepared from the genital ridges of hatching embryos were transplanted into recipients at various developmental stages. The PGCs injected into the peritoneal cavities of hatching embryos had the ability to migrate toward, and to colonize, the genital ridges of recipient embryos. Furthermore, donor-derived PGCs proliferated and differentiated into mature eggs and sperm in the allogenic gonads; the resulting gametes produced live fry, showing the donor-derived phenotype, through fertilization. Combined with in vitro culture, genetic modification, and cryopreservation of PGCs, this technique provides new approaches for fish bioengineering.

Age Factors↗
PubMed2002

Gender selection in China: its meanings and implications.

With the advancement of assisted reproduction technologies, people are offered wider choices to choose the gender of their offspring and to construct 'ideal-typed' families with specific gender structure. Gender selection is welcomed by many societies with gender-specific preference, especially those patriarchal societies such as Chinese communities. It is not only a medical procedure but also a social orientation, which reveals much of the underlying preference towards gender. This paper explores the cultural dimensions to gender selection and its psychosocial meanings and implications in Chinese societies, especially after the establishment of One Child Policy in China. Problems associated with son preference in the culture with strong gender stereotyping are addressed. We believe that gender selection for social reasons should not be allowed since undesirable outcomes will be resulted under such strict population control program.

China↗
PubMed2001

Effects of female and male smoking on success rates of IVF and gamete intra-Fallopian transfer.

BACKGROUND: Smoking by both male and female partners may play a significant role in the success rates of assisted reproductive technologies. The objective of this 5-year prospective study was to investigate the influence of cigarette smoking by the wife, husband, and couple at various time points (e.g. lifetime, week prior, or during the procedures) on different biological parameters of IVF and gamete intra-Fallopian transfer (GIFT). METHODS AND RESULTS: A total of 221 couples, aged >20 years, of Caucasian, Black, Asian or Hispanic descent were recruited from seven infertility clinics located in Southern California. Couples (i.e. either female or male or both) who ever smoked compared with non-smokers, had adjusted relative risks (RR) of 2.41 (95% CI 1.07-5.45, P = 0.03) of not achieving a pregnancy, and 3.76 (95% CI 1.40-10.03, P < 0.01) of not having a live birth delivery, while adjusting for potential confounders. For couples who smoked for >5 years, there was an adjusted RR = 4.27 of not achieving a pregnancy (95% CI l.53-11.97, P = 0.01). The number of oocytes retrieved decreased by 40% for couples (smokers, n = 6) and by 46% for men who smoked during the week of the visit for IVF or GIFT. Women who smoked in their lifetime had adjusted risks of 2.71 of not achieving a pregnancy (95% CI 1.37-5.35, P < 0.01), and 2.51 (95% CI 1.11-5.67, P < 0.03) of not having a live birth delivery. CONCLUSIONS: There is compelling evidence that couples should be made aware that smoking years before undergoing IVF and GIFT can impact treatment outcome. This study may also provide insight into the timing and effects of male and female smoking on natural reproduction.

Adult↗
PubMed2003

The presence of blood in the transfer catheter negatively influences outcome at embryo transfer.

BACKGROUND: Embryo transfer (ET) influences pregnancy rates in patients undergoing assisted reproduction. Data are conflicting as to which variables affect ET success. This study examines variables that may affect outcome after ET in assisted reproductive technology patients who had high-quality embryos transferred. METHODS: Over a 23 month period, 669 consecutive cycles were examined. Only patients having grade I and grade II embryos, or blastocyst transfers, were included in this retrospective analysis. A total of 584 consecutive cycles met study criteria. At the time of ET, the following variables were recorded: aborted first attempt at ET; presence of blood and/or mucus in or on the transfer catheter after ET; ease of ET as judged by provider; need for mock embryo transfer immediately before the actual transfer and retention of embryos in the transfer catheter. These variables were retrospectively analysed for their impact on implantation rate (IR) and clinical pregnancy rate (CPR). RESULTS: There were 290 gestations (49.7% CPR). Multiple attempts at ET, subjective difficulty of ET, performance of a sham pass immediately prior to embryo transfer, and presence of mucus on or in the catheter did not affect the CPR or IR. No difference was noted in the mean age of patients having or lacking any of these factors. There was a significant association between the presence of blood on or in the catheter and decreased IR (P = 0.015) and CPR (P = 0.004). Retained embryos also decreased IR (P = 0.03). Multivariable analysis confirmed that the presence of blood on the transfer catheter was the most important of these transfer characteristics in predicting IR (P = 0.042) and CPR (P = 0.018). CONCLUSIONS: These results suggest that when only high-grade embryos or blastocysts are transferred, the presence of blood on the catheter is associated with decreased IR and CPR in assisted reproduction.

Adult↗
PubMed2000

Role of LH and FSH in ovarian function.

Human gonadotrophin preparations have been used in the treatment of infertility for almost four decades. The earliest preparations were derived from urine from postmenopausal women and contained approximately equal amounts of follicle stimulating hormone (FSH) and luteinizing hormone (LH) activities. However, with the recognition that FSH is the principal regulator of follicular growth and maturation, these have been largely superseded by highly purified urinary FSH preparations and, more recently, recombinant human FSH (r-hFSH). Because of its complexity, r-hFSH is expressed in mammalian cells grown in culture and, from a manufacturing stand point, offers superior purity and batch-to-batch consistency, compared with urinary preparations. A number of clinical trials have compared the efficacy of r-hFSH and urinary FSH in women undergoing assisted reproductive technologies (ART). In general, these have shown that fewer FSH ampoules are required to achieve ovarian stimulation with r-hFSH, while the number of oocytes retrieved and embryos produced are higher than with urinary FSH. Additionally, the results of a recent meta-analysis have also shown that the clinical pregnancy rate per cycle started is significantly higher with r-hFSH, compared with urinary FSH. Furthermore, in poor responder patients, higher implantation rates were seen in patients treated with r-hFSH than in those treated with urinary FSH, suggesting that embryo viability is increased following use of the recombinant preparations. The finding that FSH preparations produce effective ovarian stimulation compared to human menopausal gonadotrophins in women undergoing ART raises the question of whether LH is required for ovarian stimulation. This has been investigated in a number of recent studies. For example, results have suggested that implantation rates may actually be lower in women who received exogenous LH. Such studies suggest, therefore, that in normogonadotrophic women, the addition of LH to an r-hFSH regimen does not add any further clinical benefit and may actually be detrimental. Hence, it appears that LH administration is necessary only in women with hypogonadotrophic hypogonadism. In conclusion, r-hFSH is a consistently pure and high quality gonadotrophin preparation and contributes to increasing the successful outcome of an ART cycle. Together with careful auditing of routine clinical practice, and the application of evidence-based medicine to facilitate clinical decision making, this means that a total quality management approach can be applied to optimize the outcome of assisted reproduction.

Clinical Trials as Topic↗
PubMed2002

Preservation of fertility in nature and ART.

Individuals may regard reproduction as optional but sufficient number of them must be productive to perpetuate the species. The reproductive system is surprisingly vulnerable and depends, among other things, on a limited endowment of oocytes, controlled proliferation of spermatogonial stem cells and the genetic integrity of both. The developmental competence of oocytes and spermatogonial stem cells is maintained by evolved mechanisms for cellular detoxification and genomic stability, and excess or damaged cells are eliminated by apoptosis. Gonadal failure as a result of germ cell depletion can occur at any age, and from the effects of chemical cytotoxicity, disease and infection as well as genetic predisposition. Among extrinsic factors, alkylating agents and ionizing radiation are important causes of iatrogenic gonadal failure in young women and men. In animal models, there is evidence that hormonal manipulation, deletion of genes involved in apoptotic pathways and dietary manipulation can protect against natural and induced germ cell loss, but evidence in humans is absent or unclear. Assisted reproductive technologies (ARTs) provide an ensemble of strategies for preserving fertility in patients and commercially valuable or endangered species. Semen cryopreservation was the first technology for preserving male fertility, but this cannot serve prepubertal boys, for whom banking of testicular biopsies may provide a future option. In sterilized rodents, cryopreserved spermatogonial stem cells can recolonize seminiferous tubules and reinitiate spermatogenesis, and subcutaneous implantation of intact tubules can generate spermatozoa for fertilization in vitro by intracytoplasmic sperm injection. Transplantation of frozen-banked ovarian tissue is well-established for restoring cyclicity and fertility and is currently undergoing clinical evaluation for cancer patients. When restoration of natural fertility is unnecessary or reimplantation is unsafe, it is desirable to culture the germ cells from thawed tissue in vitro until they reach the stage at which they can be fertilized. Low temperature banking of immature germ cells is potentially very versatile, but storage of embryos and, to a lesser extent, mature oocytes is already practised in a number of species, including humans, and is likely to remain a mainstay for fertility preservation.

Animals↗
PubMedDate not supplied

Multiple birth resulting from ovarian stimulation for subfertility treatment.

Assisted reproductive technologies (ARTs) aim to increase a woman's chances of becoming pregnant by bringing many female and male gametes into close proximity. Techniques to achieve this objective include ovarian hyperstimulation by maturation of several oocytes, intrauterine insemination (IUI) of concentrated sperm, or in-vitro fertilisation (IVF) by bringing gametes together outside the female body. The very nature of ovarian hyperstimulation--with or without IUI--enhances the risk of multiple pregnancy (eg, two or more babies). In most IVF cycles, more than one embryo is transferred, again resulting in an increased chance of multiple pregnancy. Developed societies have witnessed a large rise in prevalence of twin, triplet, and higher order multiple births, mainly resulting from ARTs. The primary aim of this Review is to increase awareness of the many implications of the present iatrogenic epidemic of multiple births. The background of ovarian hyperstimulation, trends supporting current practice, and strategies to reduce the chance of multiple pregnancy are highlighted.

Female↗
PubMed1991

Morality in flux: medical ethics dilemmas in the People's Republic of China.

The bioethical dilemmas receiving the most attention in China now relate to the two ends of life: birth and death. On one end are issues relating to reproductive technology, especially birth control and family planning; at the other end is euthanasia... More research and discussion among people from various fields is needed. Progress will be made one step at a time, and I recommend that we proceed now to win acceptance of brain death criteria; to make clear the distinctions between passive and active euthanasia,...to encourage the use of living wills; and to protect the interests of newborns who are not terminally ill, including those with mild defects. In the changing context of modernization, in which different and even incompatible value systems must coexist, it is best for us to approach the ethical dilemmas facing us with mutual respect and understanding.

Abortion, Eugenic↗
PubMed2003

Models for future delivery of care in infertility: the role of the private sector.

An estimated 85% of infertility treatment at the tertiary level in the UK currently is funded by the infertile couples themselves. Of the 15% of couples who receive NHS funding for assisted reproductive technology (ART), a sizeable proportion is provided by private clinics. If the National Institute of Clinical Excellence (NICE) decides that the National Health Service (NHS) should provide funding for an increased number of treatments, then it is unlikely that wholly NHS ART clinics will be able to provide the extra number of cycles required. Those private clinics in the UK that bid to provide treatment funded by the NHS through primary care trusts (PCT) generally provide a cost-effective service in a 'patient friendly' environment. The case is made in this article that ART clinics in the private sector that wish to bid for PCT contracts, should be allowed to compete on an equal basis with NHS or NHS-private combined clinics. PCTs awarding contracts should be wholly driven by good evidence of clinical effectiveness, cost effectiveness and the provision of a quality service to patients.

Adult↗
PubMed2004

Overall prognosis with current treatment of infertility.

Few reports provide pregnancy or birth rates for large groups of infertile couples having a comprehensive range of treatments. This model utilizes published evidence about diagnosis, treatment, the duration of treatment and the proportion of couples receiving treatment. Assisted reproduction technology treatment (ART) utilization was set arbitrarily at three levels: 3, 10 or 50% of the couples that had no live birth after conventional treatment. For each diagnosis and treatment the model estimated total live births, singleton live births and multiple live births per 10,000 couples. The overall live birth rate with non-ART treatment would be 37%, involving 3,725 live births, of which 3,478 (93%) would be singleton and 247 (7%) would be multiple. With ART utilization at 3, 10 and 50% of couples with persistent infertility in each diagnostic category, live birth rates were 39, 43 and 47% respectively, with 8, 10 and 12% multiple births. The corresponding utilization of ART would be 244, 813 and 1481 ART cycles per 10(6) population per annum. Typical management of infertility would fall short of 50% live births even with extensive utilization of ART. Underlying unknown untreatable factors remain barriers to greater overall success in the treatment of infertility.

Birth Rate↗
PubMed1995

Improvement of pregnancy and implantation rates in cyclic women undergoing oocyte donation after long-term down-regulation.

An oocyte donation programme was carried out in 122 patients aged between 40 and 49 years for a total of 225 replacement cycles. Eggs were donated by 103 women undergoing assisted reproduction technologies in our infertility centre. Recipients were divided into different groups according to whether they were menopausal (group A) or cyclic and treated with short- (group B) or long-term (group C) gonadotrophin-releasing hormone analogues. In group C, the ovarian suppression of the patients was prolonged with the aim of producing a type of artificial menopause. Oocyte donors were aged between 21 and 35 years, and were equally distributed between the different groups. There were significant differences in pregnancy and implantation rates according to ovarian status: 30.8 and 16.1% respectively in group A, 30.6 and 17.7% respectively in group C versus 10.4 and 5.6% respectively in group B. Apart from improved pregnancy and implantation rates in cyclic women aged > 40 years after long-term down-regulation, these data seem to demonstrate an important role for the endometrium in the implantation process.

Adult↗
PubMed2002

The art of regulation and the regulation of ART: the impact of regulation on research and clinical practice.

How a society regulates Assisted Reproduction Technologies (ART) depends on cultural context. The challenge for the regulatory regime is to balance protection for patients and society with freedom for medico-scientific creativity. Neither an exclusively market-regulated nor a peer-regulated approach is realistic politically, or desirable socially, ethically and legally. Legitimate social issues that go beyond the exclusive expertise of doctors and scientists or market choice by patients need to be accommodated within the regulatory regime. Within this context, four key issues are discussed: the lack of a shared social ethic that helps the needs of the community to be balanced against those of its individual members; the negative impact of intrusive external regulation on scientists and doctors; the requirement for doctors and scientists to review their professional structures reflectively and critically if they are to be entrusted with peer-regulation; and the desirability of constructive dialogue between regulators and regulated rather than the use of coercion and criminal sanctions.

Australia↗